Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients

This study was designed to evaluate irinotecan (CPT-11) disposition and pha rmacodynamics in the presence and absence of the broad-spectrum antibiotic neomycin, Seven evaluable cancer patients experiencing diarrhea graded grea ter than or equal to2 after receiving CPT-11 alone (350 mg/m(2) i.v. once e very 3 weeks) received the same dose combined with oral neomycin at 1000 mg three times per day (days -2 to 5) in the second course. Neomycin had no e ffect on the systemic exposure of CPT-11 and its major metabolites (P great er than or equal to 0.22), However, it changed fecal beta -glucuronidase ac tivity from 7.03 +/- 1.76 mug/h/mg (phenolphthalein assay) to undetectable levels and decreased fecal concentrations of the pharmacologically active m etabolite SN-38, Although neomycin had no significant effect on hematologic al toxicity (P > 0.05), diarrhea ameliorated in six of seven patients (P = 0.033). Our findings indicate that bacterial beta -glucuronidase plays a cr ucial rot in CPT-11-induced diarrhea without affecting entero-cycling and s ystemic SN-38 levels.